Observations on transmitter release at the squid giant synapse have been used as the basis for a new hypothesis for exocytosis, termed the "ion channel model." The key feature of this model is the presence of a Ca-activated K channel and an anion channel on the secretory vesicle membrane. According to the model, the entry of Ca into the cytoplasm activates the K channel, allowing K ions to enter the vesicle and anions follow down their electro-chemical gradient. The resulting accumulation of ions in the vesicle increases its osmotic pressure, leading to water entry, vesicle expansion and, finally, fusion of the vesicle with the cell membrane. This model can account for key features of exocytosis in synaptic transmission such as the fourth power dependence of secretion on external Ca, the very short latency between Ca entry and activation of the release mechanism, and the phenomenon of facilitation. Our first test of the ion channel model has been to search for the postulated ion channels in the vesicle membrane by incorporating purified secretory vesicles into artificial membranes. In support of the model, we have identified both a Ca-activated K permeable channel and an anion channel associated with these secretory vesicles.